Role of dorsal hippocampal cannabinoid receptors and nitric oxide in anxiety like behaviours in rats using the elevated plus-maze test

1. The important role of the cannabinoid system in the modulation of anxiety like behaviours in clinical and experimental studies has been proposed. However, investigations into this effect of cannabinoids has produced contradictory results. It has been reported that different neurotransmitters, such as nitric oxide (NO), are involved in the behavioural effects of cannabinoids. The hippocampus is also an important brain region in the modulation of anxiety in which CB1 receptors are densely expressed. The present study was designed to evaluate the interactions between cannabinoid and NO systems in the CA1 brain region of the rats using the plus-maze test. 2. Rats were anaesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week recovery, the effects of intra-CA1 administration of WIN55212-2 (1, 2.5 and 5 mu g/rat), AM251 (2, 10 and 50 ng/rat), L-arginine (0.01, 0.1 and 1 mu g/rat) and N-G-nitro-L-arginine methyl ester (L-NAME; 1, 10 and 100 ng/rat) on percentage open arm time (%OAT) and percentage open arm entries (%OAE) were determined. Moreover, the effects of pretreatment with AM251 (2 ng/rat), L-arginine (0.01 mu g/rat) and L-NAME (1 ng/rat) on the response induced by intra-CA1 administration of WIN55212-2 were also assessed. 3. The administration of either L-arginine or L-NAME into the CA1 region produced significant anxiogenic-like responses, whereas administration of AM251 induced anxiolytic effects. Intra-CA1 injection of WIN55212-2 produced a significant anxiogenic-like effect that was reversed by AM251 and was also altered by L-NAME, but not by L-arginine. 4. These data imply that cannabinoids may have anxiogenic-like effects in the CA1 region of the hippocampus in which CB1 receptors and NO may be involved.